Detection of genetic loci associated with plasma fetuin-A: A meta-analysis of genome-wide association studies from the CHARGE Consortium

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Detection of genetic loci associated with plasma fetuin-A : A meta-analysis of genome-wide association studies from the CHARGE Consortium. / Jensen, Majken K.; Jensen, Richard A.; Mukamal, Kenneth J.; Guo, Xiuqing; Yao, Jie; Sun, Qi; Cornelis, Marilyn; Liu, Yongmei; Chen, Ming Huei; Kizer, Jorge R.; Djoussé, Luc; Siscovick, David S.; Psaty, Bruce M.; Zmuda, Joseph M.; Rotter, Jerome I.; Garcia, Melissa; Harris, Tamara; Chen, Ida; Goodarzi, Mark O.; Nalls, Michael A.; Keller, Margaux; Arnold, Alice M.; Newman, Anne B.; Hoogeveen, Ron C.; Rexrode, Kathryn M.; Rimm, Eric B.; Hu, Frank B.; Ramachandran, Vasan S.; Katz, Ronit; Pankow, James S.; Ix, Joachim H.

I: Human Molecular Genetics, Bind 26, Nr. 11, 01.01.2017, s. 2156-2163.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Jensen, MK, Jensen, RA, Mukamal, KJ, Guo, X, Yao, J, Sun, Q, Cornelis, M, Liu, Y, Chen, MH, Kizer, JR, Djoussé, L, Siscovick, DS, Psaty, BM, Zmuda, JM, Rotter, JI, Garcia, M, Harris, T, Chen, I, Goodarzi, MO, Nalls, MA, Keller, M, Arnold, AM, Newman, AB, Hoogeveen, RC, Rexrode, KM, Rimm, EB, Hu, FB, Ramachandran, VS, Katz, R, Pankow, JS & Ix, JH 2017, 'Detection of genetic loci associated with plasma fetuin-A: A meta-analysis of genome-wide association studies from the CHARGE Consortium', Human Molecular Genetics, bind 26, nr. 11, s. 2156-2163. https://doi.org/10.1093/hmg/ddx091

APA

Jensen, M. K., Jensen, R. A., Mukamal, K. J., Guo, X., Yao, J., Sun, Q., Cornelis, M., Liu, Y., Chen, M. H., Kizer, J. R., Djoussé, L., Siscovick, D. S., Psaty, B. M., Zmuda, J. M., Rotter, J. I., Garcia, M., Harris, T., Chen, I., Goodarzi, M. O., ... Ix, J. H. (2017). Detection of genetic loci associated with plasma fetuin-A: A meta-analysis of genome-wide association studies from the CHARGE Consortium. Human Molecular Genetics, 26(11), 2156-2163. https://doi.org/10.1093/hmg/ddx091

Vancouver

Jensen MK, Jensen RA, Mukamal KJ, Guo X, Yao J, Sun Q o.a. Detection of genetic loci associated with plasma fetuin-A: A meta-analysis of genome-wide association studies from the CHARGE Consortium. Human Molecular Genetics. 2017 jan. 1;26(11):2156-2163. https://doi.org/10.1093/hmg/ddx091

Author

Jensen, Majken K. ; Jensen, Richard A. ; Mukamal, Kenneth J. ; Guo, Xiuqing ; Yao, Jie ; Sun, Qi ; Cornelis, Marilyn ; Liu, Yongmei ; Chen, Ming Huei ; Kizer, Jorge R. ; Djoussé, Luc ; Siscovick, David S. ; Psaty, Bruce M. ; Zmuda, Joseph M. ; Rotter, Jerome I. ; Garcia, Melissa ; Harris, Tamara ; Chen, Ida ; Goodarzi, Mark O. ; Nalls, Michael A. ; Keller, Margaux ; Arnold, Alice M. ; Newman, Anne B. ; Hoogeveen, Ron C. ; Rexrode, Kathryn M. ; Rimm, Eric B. ; Hu, Frank B. ; Ramachandran, Vasan S. ; Katz, Ronit ; Pankow, James S. ; Ix, Joachim H. / Detection of genetic loci associated with plasma fetuin-A : A meta-analysis of genome-wide association studies from the CHARGE Consortium. I: Human Molecular Genetics. 2017 ; Bind 26, Nr. 11. s. 2156-2163.

Bibtex

@article{c970a93d82fe48f1b99afcfaccba2b1b,
title = "Detection of genetic loci associated with plasma fetuin-A: A meta-analysis of genome-wide association studies from the CHARGE Consortium",
abstract = "Plasma fetuin-A is associated with type 2 diabetes, and AHSG, the gene encoding fetuin-A, has been identified as a susceptibility locus for diabetes and metabolic syndrome. Thus far, unbiased investigations of the genetic determinants of plasma fetuin-A concentrations have not been conducted. We searched for single nucleotide polymorphisms (SNPs) related to fetuin- A concentrations by a genome-wide association study in six population-based studies. We examined the association of fetuin-A levels with ~ 2.5 million genotyped and imputed SNPs in 9,055 participants of European descent and 2,119 African Americans. In both ethnicities, the strongest associations were centered in a region with a high degree of LD near the AHSG locus. Among 136 genome-wide significant (P < 0.05 × 10-8) SNPs near the AHSG locus, the top SNP was rs4917 (P=1.27×10-303), a known coding SNP in exon 6 that is associated with a 0.06 g/l (~13%) lower fetuin-A level. This variant alone explained 14% of the variation in fetuin-A levels. Analyses conditioned on rs4917 indicated that the strong association with the AHSG locus stems from additional independent associations of multiple variants among European Americans. In conclusion, levels of fetuin-A in plasma are strongly associated with SNPs in its encoding gene, AHSG, but not elsewhere in the genome. Given the strength of the associations observed for multiple independent SNPs, the AHSG gene is an example of a candidate locus suitable for additional investigations including fine mapping to elucidate the biological basis of the findings and further functional experiments to clarify AHSG as a potential therapeutic target.",
author = "Jensen, {Majken K.} and Jensen, {Richard A.} and Mukamal, {Kenneth J.} and Xiuqing Guo and Jie Yao and Qi Sun and Marilyn Cornelis and Yongmei Liu and Chen, {Ming Huei} and Kizer, {Jorge R.} and Luc Djouss{\'e} and Siscovick, {David S.} and Psaty, {Bruce M.} and Zmuda, {Joseph M.} and Rotter, {Jerome I.} and Melissa Garcia and Tamara Harris and Ida Chen and Goodarzi, {Mark O.} and Nalls, {Michael A.} and Margaux Keller and Arnold, {Alice M.} and Newman, {Anne B.} and Hoogeveen, {Ron C.} and Rexrode, {Kathryn M.} and Rimm, {Eric B.} and Hu, {Frank B.} and Ramachandran, {Vasan S.} and Ronit Katz and Pankow, {James S.} and Ix, {Joachim H.}",
year = "2017",
month = jan,
day = "1",
doi = "10.1093/hmg/ddx091",
language = "English",
volume = "26",
pages = "2156--2163",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "11",

}

RIS

TY - JOUR

T1 - Detection of genetic loci associated with plasma fetuin-A

T2 - A meta-analysis of genome-wide association studies from the CHARGE Consortium

AU - Jensen, Majken K.

AU - Jensen, Richard A.

AU - Mukamal, Kenneth J.

AU - Guo, Xiuqing

AU - Yao, Jie

AU - Sun, Qi

AU - Cornelis, Marilyn

AU - Liu, Yongmei

AU - Chen, Ming Huei

AU - Kizer, Jorge R.

AU - Djoussé, Luc

AU - Siscovick, David S.

AU - Psaty, Bruce M.

AU - Zmuda, Joseph M.

AU - Rotter, Jerome I.

AU - Garcia, Melissa

AU - Harris, Tamara

AU - Chen, Ida

AU - Goodarzi, Mark O.

AU - Nalls, Michael A.

AU - Keller, Margaux

AU - Arnold, Alice M.

AU - Newman, Anne B.

AU - Hoogeveen, Ron C.

AU - Rexrode, Kathryn M.

AU - Rimm, Eric B.

AU - Hu, Frank B.

AU - Ramachandran, Vasan S.

AU - Katz, Ronit

AU - Pankow, James S.

AU - Ix, Joachim H.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Plasma fetuin-A is associated with type 2 diabetes, and AHSG, the gene encoding fetuin-A, has been identified as a susceptibility locus for diabetes and metabolic syndrome. Thus far, unbiased investigations of the genetic determinants of plasma fetuin-A concentrations have not been conducted. We searched for single nucleotide polymorphisms (SNPs) related to fetuin- A concentrations by a genome-wide association study in six population-based studies. We examined the association of fetuin-A levels with ~ 2.5 million genotyped and imputed SNPs in 9,055 participants of European descent and 2,119 African Americans. In both ethnicities, the strongest associations were centered in a region with a high degree of LD near the AHSG locus. Among 136 genome-wide significant (P < 0.05 × 10-8) SNPs near the AHSG locus, the top SNP was rs4917 (P=1.27×10-303), a known coding SNP in exon 6 that is associated with a 0.06 g/l (~13%) lower fetuin-A level. This variant alone explained 14% of the variation in fetuin-A levels. Analyses conditioned on rs4917 indicated that the strong association with the AHSG locus stems from additional independent associations of multiple variants among European Americans. In conclusion, levels of fetuin-A in plasma are strongly associated with SNPs in its encoding gene, AHSG, but not elsewhere in the genome. Given the strength of the associations observed for multiple independent SNPs, the AHSG gene is an example of a candidate locus suitable for additional investigations including fine mapping to elucidate the biological basis of the findings and further functional experiments to clarify AHSG as a potential therapeutic target.

AB - Plasma fetuin-A is associated with type 2 diabetes, and AHSG, the gene encoding fetuin-A, has been identified as a susceptibility locus for diabetes and metabolic syndrome. Thus far, unbiased investigations of the genetic determinants of plasma fetuin-A concentrations have not been conducted. We searched for single nucleotide polymorphisms (SNPs) related to fetuin- A concentrations by a genome-wide association study in six population-based studies. We examined the association of fetuin-A levels with ~ 2.5 million genotyped and imputed SNPs in 9,055 participants of European descent and 2,119 African Americans. In both ethnicities, the strongest associations were centered in a region with a high degree of LD near the AHSG locus. Among 136 genome-wide significant (P < 0.05 × 10-8) SNPs near the AHSG locus, the top SNP was rs4917 (P=1.27×10-303), a known coding SNP in exon 6 that is associated with a 0.06 g/l (~13%) lower fetuin-A level. This variant alone explained 14% of the variation in fetuin-A levels. Analyses conditioned on rs4917 indicated that the strong association with the AHSG locus stems from additional independent associations of multiple variants among European Americans. In conclusion, levels of fetuin-A in plasma are strongly associated with SNPs in its encoding gene, AHSG, but not elsewhere in the genome. Given the strength of the associations observed for multiple independent SNPs, the AHSG gene is an example of a candidate locus suitable for additional investigations including fine mapping to elucidate the biological basis of the findings and further functional experiments to clarify AHSG as a potential therapeutic target.

U2 - 10.1093/hmg/ddx091

DO - 10.1093/hmg/ddx091

M3 - Journal article

C2 - 28379451

AN - SCOPUS:85027369881

VL - 26

SP - 2156

EP - 2163

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 11

ER -

ID: 244626716